Abstract
Stimulation of many cell types with their agonists leads to the generation of two intracellular messengers, diacylglycerol and inositol trisphosphate (IP3) derived from hydrolysis of phosphatidylinositol bisphosphate by polyphosphoinositide phosphodiesterase (PPI-pde) in the membrane. PPI-pde is coupled to receptors by a putative G-protein, Gp. PPI-pde activity and β-glucuronidase secretion can be measured simultaneously in permeabilized undifferentiated HL60 cells stimulated by Ca2+ and guanine nucleotides. The effect of GTPyS on secretion could be explained by its ability to generate IP3 and diacylglycerol, an activator of protein kinase C. However, when increased intracellular Ca2+ mobilized by IP3 is buffered, the phorbol ester, phorbol 12-myristate 13-acetate (PMA), a potent and stable activator of protein kinase C, does not fully substitute for GTPyS. The effects of PMA are (1) to increase the sensitivity to Ca2+, (2) to dramatically increase secretion in the presence of GTPyS at nanomolar concentrations of Ca2+, (3) to promote some secretion in the presence of Ca2+ alone and (4) to inhibit PPI- pde activity. PPI-pde activity stimulated by both GTPyS and Ca2+ alone was inhibited by pretreatment of the cells with PMA. Under these conditions, secretion of (β-glucuronidase was increased. The dissociation between PPI-pde activity and secretion implicates the existence of a further G-protein, Ge, in the stimulus- secretion pathway.
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© 1989 Springer-Verlag Berlin Heidelberg
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Stutchfield, J., Geny, B., Cockcroft, S. (1989). The Role of G-Proteins in Exocytosis. In: Evangelopoulos, A.E., Changeux, J.P., Packer, L., Sotiroudis, T.G., Wirtz, K.W.A. (eds) Receptors, Membrane Transport and Signal Transduction. NATO ASI Series, vol 29. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74200-2_9
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DOI: https://doi.org/10.1007/978-3-642-74200-2_9
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